The new year has started with some pleasing clinical trial news for the Parkinson’s community: The results of the “Ambroxol in Disease Modification in Parkinson Disease” (AiM-PD study) have been published.
This is a clinically available drug that is used for the treatment of respiratory issues, which researchers are re-purposing for Parkinson’s based on some interesting properties the drug has.
The results of the clinical trial suggest that ambroxol was safe and well tolerated in people with Parkinson’s for the length of the 6 month study. It accessed the brain and increased levels of target proteins while there.
In today’s post, we will discuss what ambroxol is, what research has been conducted on it, and what the results of this study suggest.
The author of this blog is the deputy director of research at The Cure Parkinson’s Trust, and as such he feels that it is necessary to start this post with a very clear declaration – FULL DISCLOSURE: The Cure Parkinson’s Trust (in partnership with the Van Andel Institute) was a funder of the ambroxol clinical trial which is going to be discussed in this post.
Right. That said, let’s try and do a completely unbiased review of the ambroxol trial results 🙂
In one particular SoPD post last year we discussed the Linked Clinical Trials initiative, which is an international program that was set up 8 years ago with the goal of rapidly repurposing clinically available drugs exhibiting disease modifying potential in models of Parkinson’s (Click here to read the previous SoPD post on this topic).
What is meant by repurposing?
Drug repurposing (repositioning, reprofiling or re-tasking) is a strategy of identifying novel uses for clinically approved drugs that fall outside the scope of the original medical indication.
An example of this is “Viagra”.
It was originally developed as an anti-hypertensive medication, but was hugely more successful in the treatment of erectile dysfunction.
The strategy has been adopted and applied by many organisations because it allows for the by-passing of large parts of the drug discovery process, saving time and resources in getting new treatments to the clinic.
By repurposing a clinically approved drug – for which we may know a great deal about already in terms of safety, tolerability and dose range – we can skip large parts of the clinical trial process and jump straight to testing the drug in our population of interest (in this case people with Parkinson’s).
And this is what the Linked Clinical Trials (or LCT) program was set up to do in Parkinson’s.
The first drug that was prioritised by the LCT committee for repurposing was a diabetes drug called exenatide (also known as Bydureon).
It is fair to say this LCT-initiated clinical trial program has provided interesting results thus far (Click here and here to read a SoPD post on this) and the exenatide program is now entering Phase III testing in Parkinson’s (Click here to read more about the Phase III trial).
In late 2014, the LCT committee prioritised another clinically available drug for repurposing to Parkinson’s.
That drug is called ambroxol.
What is ambroxol?
Here at the SoPD, we are primarily interested in disease modification for Parkinson’s. While there is a great deal of interesting research exploring the causes of the condition, novel symptomatic therapies, and other aspects of Parkinson’s, my focus is generally on the science seeking to slow, stop or reverse the condition.
At the start of each year, it is a useful practise to layout what is planned and what we will be looking for over the next 12 months. Obviously, where 2020 will actually end is unpredictable, but an outline of what is scheduled over the next year will hopefully provide us with a useful resource for better managing expectations.
In this post, I will try to lay out some of what 2020 holds for us with regards to clinical research focused on disease modification for Parkinson’s.
Lord Robert Baden-Powell. Source: Utahscouts
My old scout master once looked around our horse shoe, making eye contact with each of us, before asking the question:
“When did Noah build the ark?”
My fellow scouts and I looked at each other – confused. Did he want an exact date?!?
The scout master waited a moment for one of us to offer up some idiotic attempt at an answer – thankfully no one did – before he solemnly said:
“Before the rain”
It was one of those childhood moments that made little sense at the time, but comes back to haunt you as an adult when you are looking at what the future may hold and trying to plan for it.
# # # # # # # # # # #
Today’s post is our annual horizon scanning effort, where we lay out what is on the cards for the next 12 months with regards to clinical research focused on disease modification in Parkinson’s.
We will also briefly mention other bits and pieces of preclinical work that we are keeping an eye on for any news of development.
To be clear, this post is NOT intended to be an exercise in the reading of tea leaves – no predictions will be made here. Nor is this a definitive or exhaustive guide of what the next year holds for disease modification research (if you see anything important that I have missed – please contact me). And it should certainly not be assumed that any of the treatments mentioned below are going to be silver bullets or magical elixirs that are going to “cure” the condition.
In the introduction to last year’s outlook, I wrote of the dangers of having expectations (Click here to read that post). I am not going to repeat that intro here, but that the same message applies as we look ahead to what 2020 holds.
In fact, it probably applies even more for 2020, than it did for 2019.
2020 is going to be a busy year for Parkinson’s research, and I am genuinely concerned that posts like this are only going to raise expectations. My hope is that a better understanding of where things currently are and what is scheduled for the next 12 months will help in better managing those expectations. Please understand that there is still a long way to go for all of these experimental therapies.
All of that said, let’s begin:
Novel therapies are increasing being developed to focus on specific subtypes of Parkinson’s. The hope is that if they work on one type of Parkinson’s, then maybe they will also work on others.
Many of these new experimental treatments are focused on specific genetic subtypes of the condition, which involve having a specific genetic variation that increases one’s risk of developing Parkinson’s.
Increasing amounts of data, however, are accumulating that some of the biological pathways affected by these genetic variations, are also dysfunctional in people with sporadic (or idiopathic) Parkinson’s – where a genetic variation can not explain the abnormality.
In today’s post, we will review some new research that reports reductions in a specific Parkinson’s-associated biological pathway, and discuss what it could mean for future treatment of the Parkinson’s.
I was recently at a conference on Parkinson’s research where a prominent scientist reminded the audience that just because a person with Parkinson’s carries certain genetic risk factor (an error in a region of their DNA that increases their risk of developing Parkinson’s), does not mean that their Parkinson’s is attributable that genetic variation. Indeed, lots of people in the general population carry Parkinson’s associated genetic risk factors, but never go on to develop the condition.
And this is a really important idea for the Parkinson’s community to understand: Most of the genetics of Parkinson’s deals with ‘association’, not with ‘causation’.
But that begs the question ‘if we do not know that these errors in our DNA are causing Parkinson’s, then why should we be trying to develop therapies based on their biology?’
It is a fair question (it is also a very deep and probing question to start a post off with!).
The genetics of Parkinson’s has been extremely instructive in providing us with insights into the potential underlying biology of the condition. We have learnt a great deal about what many of the biological processess thatare associated with these genetic risk factors, and (yes) various experimental therapies have been developed to target them.
These novel treatments are clinically tested in the hope that they will have beneficial effects not just on individuals carrying certain genetic risk factors, but also on the wider Parkinson’s community.
And recently, there has been increasing evidence supporting this possibility. Some of the biological pathways associated with these genetic mutations appear to also be abnormal in people with Parkinson’s who do not carry the genetic variation.
What do you mean?
Things were a bit quiet on the SoPD over the summer, but for good reasons. There was a short hiatus for a family break, but the rest of the time I was rather occupied with the day job. Tremendous efforts were being made at the Cure Parkinson’s Trust, as we were gearing up for our main event of the year: the Linked Clinical Trials (LCT) meeting.
This is an annual meeting at which 20 Parkinson’s experts from around the world, gather for a two day face-to-face pow-wow. They evaluate dossiers which contain everything we know about 20+ compounds which have exhibited potential for disease modification in Parkinson’s. The goal of the committee is to decide which of them is ready for clinical evaluation.
The writing of those LCT dossiers is a year long exercise, which inevitably becomes a bit of a panic in June and July (hence the lack of activity here at SoPD HQ during that period). It is a mammoth, marathon task, but as you shall see it is one that I rather like.
In today’s post, we will discuss what the Linked Clinical Trials initiative is, the process behind the project, and some of the progress being made by the programme.
Archimedes. Source: Lecturesbureau
Archimedes of Syracuse (287 BC – 212 BC) the ancient Greek mathematician, once said that the “shortest distance between two points is a straight line“.
My dad (who is not a regular readers of this blog, but is possibly on par with Archie – just in case he does ever read this) has often been heard saying “Just get to the point Simon“.
Millennia apart, but their collective wisdom is same: Ignore everything else, and get straight to the heart of the matter as quickly as you can.
And this is one of the aspect I really like about the Linked Clinical Trials initiative.
It is all about getting to potentially disease modifying treatments for Parkinson’s to the community as quickly as possible.
What is the Linked Clinical Trials programme?
The recent documents filed with the U.S. Securities and Exchange Commission by the biotech firm Prevail Therapeutics provides interesting insight into the bold plans of this company which was only founded in 2017.
Even more recent news that the U.S. Food and Drug Administration (FDA) has accepted the company’s Investigational New Drug (IND) application for its lead experimental treatment – PR001 – suggests that this company is not wasting any time.
PR001 is a gene therapy approach targeting GBA-associated Parkinson’s.
In today’s post, we will discuss what GBA-associated Parkinson’s is, how Prevail plans to treat this condition, and discuss what we know about PR001.
Caterina Fake. Source: TwiT
The title of this post comes is from a quote by Caterina Fake (co-founder of Flickr and Hunch (now part of Ebay)), but it seemed appropriate.
This post is all about dreaming big (curing Parkinson’s), the struggle to get the research right, and to create a biotech company: Prevail Therapeutics.
What is Prevail Therapeutics?
Prevail is a gene therapy biotech firm that was founded in 2017.
Dr Asa Abeliovich. Source: Prevail
It was set up in a collaborative effort with The Silverstein Foundation for Parkinson’s with GBA (Click here to read a previous SoPD post about this organisation) and OrbiMed (a healthcare-dedicated investment firm).
What does Prevail Therapeutics do?
On the 26-31st March, the 14th International Conference on Alzheimer’s and Parkinson’s Diseases (or ADPD meeting) was held in Lisbon, Portugal.
For 5 days – between 8:30am and 7:30pm each day – over 4000 researchers were able to attend lectures of new results and ideas, in any of 8 different auditoriums. Alternatively, they could wander among hundreds of research posters.
It was a marathon effort, however, for all attendees. And a great deal of new results were shared.
In today’s post, we will discussed what was presented at the 2019 ADPD meeting and what was actually learnt.
Lisbon. Source: stmed
Lisbon is a city, midway down the western coast of the Iberian Peninsula.
It is home to a little over 500,000 people (3 million in the wider metropolitan area), and it serves as the capital city for the Portuguese people.
The Castelo de Sao Jorge, rises above Lisbon. Source: Wikipedia
Interestingly, it is the 2nd oldest European capital city (after Athens), and has had a rich and fascinating history given its strategic location. But on the 1st November 1755, 20% of the population were killed and 85% of the city’s structures were destroyed by a terrible earthquake and subsequent tsunami, which resulted in the vast majority of the city being rebuilt.
The ‘new city’ is laid out in bairros de Lisboa (neighbourhoods of Lisbon) across a hilly landscape, providing views of the River Tagus at every vantage point. And while walking the steep cobblestoned streets is delightful, there is a system of vintage public trams that can take a lot of the leg work out of the effort.
During the last week of March 2019, Lisbon was the site of the ADPD meeting.
What is the ADPD meeting?
Over the last 12 months, the Silverstein Foundation has quickly established itself as a major focused force in the fight against Parkinson’s.
And when I say ‘focused’, I mean ‘focused’ – the foundation is “actively pursues and invests in cutting edge research with the goal of discovering new therapies for the treatment of Parkinson’s Disease in glucocerebrosidase (GBA) mutation carriers”.
But the output of this effort may well have major benefits for the entire Parkinson’s community.
In today’s post, we will discuss what GBA is, how it functions inside cells, its association with Parkinson’s, and what all of this GBA focused research being funded by the Silverstein Foundation could mean for the Parkinson’s community.
Jonathan Silverstein. Source: Forbes
This is Jonathan Silverstein.
He’s a dude.
He is also a General Partner and a Co-Head of Global Private Equity at OrbiMed – the world’s largest fully dedicated healthcare fund manager. During his time at OrbiMed, the company has invested in healthcare companies that have been involved with over 60 FDA approved products.
In February 2017, he was diagnosed with Parkinson’s disease at just 49 years of age.
Rather than simply accepting this diagnosis, however, Mr Silverstein decided to apply the skills that he has built over a long and successful career in funding biotech technology, and in March 2017, he and his wife, Natalie, set up the Silverstein Foundation.
They raised $6 million from donors and then provided another $10 million of their own money to fund the endeavour, which has funded a dozen research projects and started a new company called Prevail Therapeutics (we’ll come back to this shortly).
The foundation has just one mission: “to actively pursue and invest in cutting edge research with the goal of discovering new therapies for the treatment of Parkinson’s Disease in GBA mutation carriers”
And it seeks to address this by achieving three goals:
- to find a way to halt the progression of Parkinson’s with GBA.
- to identify regenerative approaches to replace the damaged/lost cells
- to find preventative measures
What is ‘GBA’?
Today’s (experimental) post provides something new – an overview of some of the major bits of Parkinson’s-related research that were made available in January 2018.
In January of 2018, the world was rocked by news that New Zealand had become the 11th country in the world to put a rocket into orbit (no really, I’m serious. Not kidding here – Click here to read more). Firmly cementing their place in the rankings of world superpowers. In addition, they became only the second country to have a prime minister get pregnant during their term in office (in this case just 3 months into her term in office – Click here to read more about this).
In major research news, NASA and NOAA announced that 2017 was the hottest year on record globally (without an El Niño), and among the top three hottest years overall (Click here for more on this), and scientists in China reported in the journal Cell that they had created the first monkey clones, named Zhong Zhong and Hua Hua (Click here for that news)
Zhong Zhong the cute little clone. Source: BBC
New research published in the last week provides further experimental support for numerous clinical trials currently being conducted, including one by the biotech company Sanofi Genzyme.
Researchers have demonstrated that tiny proteins which usually reside on the outer wall of cells could be playing an important role in the protein clustering (or aggregation) that characterises Parkinson’s.
In today’s post we will look at this new research and discuss what it could mean for the on going clinical trials for Parkinson’s.
The proverb ‘When the cat is away, the mice will play’ has Latin origins.
Dum felis dormit, mus gaudet et exsi litantro (or ‘When the cat falls asleep, the mouse rejoices and leaps from the hole’)
It was also used in the early fourteenth century by the French: Ou chat na rat regne (‘Where there is no cat, the rat is king’).
And then Will Shakespeare used it in Henry the Fifth(1599), Act I, Scene II:
Westmoreland, speaking with King Henry V, Gloucester, Bedford, Exeter and Warwick
“But there’s a saying very old and true,
‘If that you will France win,
Then with Scotland first begin:’
For once the eagle England being in prey,
To her unguarded nest the weasel Scot
Comes sneaking and so sucks her princely eggs,
Playing the mouse in absence of the cat,
To tear and havoc more than she can eat”
Interesting. But what does any of this have to do with Parkinson’s?
The great ice hockey player Wayne Gretzky once said “A good hockey player plays where the puck is. A great hockey player plays where the puck is going to be” (the original quote actually came from his father, Walter).
At the start of each year, it is a useful practise to layout what is planned for the next 12 months. This can help us better anticipate where ‘the puck’ will be, and allow us to prepare for things further ahead.
2017 was an incredible year for Parkinson’s research, and there is a lot already in place to suggest that 2018 is going to be just as good (if not better).
In this post, we will lay out what we can expect over the next 12 months with regards to the Parkinson’s-related clinical trials research of new therapies.
Charlie Munger (left) and Warren Buffett. Source: Youtube
Many readers will be familiar with the name Warren Buffett.
The charming, folksy “Oracle of Omaha” is one of the wealthiest men in the world. And he is well known for his witticisms about investing, business and life in general.
Warren Buffett. Source: Quickmeme
He regularly provides great one liners like:
“We look for three things [in good business leaders]: intelligence, energy, and integrity. If they don’t have the latter, then you should hope they don’t have the first two either. If someone doesn’t have integrity, then you want them to be dumb and lazy”
“Work for an organisation of people you admire, because it will turn you on. I always worry about people who say, ‘I’m going to do this for ten years; and if I really don’t like it very much, then I’ll do something else….’ That’s a little like saving up sex for your old age. Not a very good idea”
“Choosing your heroes is very important. Associate well, marry up and hope you find someone who doesn’t mind marrying down. It was a huge help to me”
Mr Buffett is wise and a very likeable chap.
Few people, however, are familiar with his business partner, Charlie Munger. And Charlie is my favourite of the pair.